The compound 1-[4(S)-azido-2(S),3(R)-dihydroxy-4-(hydroxymethyl)-1(R)-cyclopentyl]cytosine I is a potent antiviral agent. (U.S. patent application Ser. No. 10/167,106 file Jun. 11, 2002; J. G. Moffatt, In Nucleoside Analogs; R. T. Walker, E. DeClercq and F. Eckstein, Eds., Plenum Publishing, New York, 1979, p144; H. Maag et al., J. Med. Chem. 1992 35:1440-1451). While biological activity is a sine non qua for an effective drug, the compound must be capable of large scale manufacturing and the physical properties of the compound can markedly impact the effectiveness and cost of a formulated active ingredient. Although it possesses potent antiviral activity, use of the free base I is limited by its thermal instability, poor crystallinity and hygroscopicity which create challenging handling and formulating problems. 
Salts of acidic and basic compounds can alter or improve the physical properties of a parent compound. These salt forming agents, however, must be identified empirically by the pharmaceutical chemist since there is no reliable method to predict the influence of a salt species on the behavior of a parent compound in dosage forms. Effective screening techniques, which potentially could simplify the selection process, are unfortunately absent (G. W. Radebaugh and L. J. Ravin Preformulation. In, Remington: The Science and Practice of Pharmacy; A. R. Gennaro Ed.; Mack Publishing Co. Easton, Pa., 1995; pp 1456-1457).
Different polymorphic forms of salts are frequently encountered among pharmaceutically useful compounds. Polymorphism is the ability of any element or compound to crystallize as more than one distinct crystalline species. Physical properties including solubility, melting point, density, hardness, crystalline shape and stability can be quite different for different polymorphic forms of the same chemical compound.
Polymorphic forms are characterized by scattering techniques, e.g., x-ray diffraction powder pattern, by spectroscopic methods, e.g., infa-red, 13C nuclear magnetic resonance spectroscopy and by thermal techniques, e.g, differential scanning calorimetry or differential thermal analysis. The compound of this invention is best characterized by the X-ray powder diffraction pattern determined in accordance with procedures which are known in the art. For a discussion of these techniques see J. Haleblian, J. Pharm. Sci. 1975 64:1269-1288, and J. Haleblain and W. McCrone, J. Pharm. Sci. 1969 58:911-929. Although the intensities of peaks in the x-ray powder diffraction patterns of different batches of the hemisulfate Ia may vary slightly, the peaks and the peak locations are characteristic for a specific polymorphic form.
The problem which must be solved is to identify a suitable salt which (i) possesses adequate chemical stability during the manufacturing process, (ii) is efficiently prepared, purified and recovered, (ii) provides acceptable solubility in pharmaceutically acceptable solvents, (iii) is amenable to manipulation (e.g. flowability and particle size) and formulation with negligible decomposition or change of the physical and chemical characteristics of the compound, (iv) exhibits acceptable chemical stability in the formulation. In addition, salts containing a high molar percent of the active ingredient are highly desireable since they minimize the quantity of material which must be formulated and administered to produce a therapeutically effective dose. These often conflicting requirements make identification suitable salts a challenging and important problem which must be solved by the skilled pharmaceutical scientist before drug development can proceed in earnest.